Method for producing long-chain glycine-N,N-diacetic acid derivatives

ABSTRACT

A process for preparing compounds of the formula IIb                    
      where R is C 6 -C 30 -alkyl or C 6 -C 30 -alkenyl, which may additionally have upto 5 hydroxyl groups, formyl groups, C 1 -C 4 -alkoxy groups, phenoxy groups or C 1 -C 4 -alkoxycarbonyl groups as substituents and may be interrupted by upto 5 nonadjacent oxygen atoms, or alkoxylate groups of the formula —(CH 2 ) k —O—(A 1 O) m —(A 2 O) n —Y where A 1  and A 2  are, independently of one another, 1,2-alkylene groups having 2 to 4 carbon atoms, Y is hydrogen, C 1 -C 12 -alkyl, phenyl or C 1 -C 4 -alkoxycarbonyl, and k is 1, 2 or 3, and m and n are each numbers from 0 to 50, and the total of m+n must be at least 4, 
     by reacting iminodiacetonitrile with aldehydes of the formula R—CHO and HCN or alkali metal cyanides, the process being carried out 
     a) in the absence of an organic solvent and in the presence of a Lewis or Brönsted acid, or 
     b) in the presence or absence of an organic solvent and in the presence of an emulsifier, or 
     c) in the presence or absence of an organic solvent and under a pressure in the range from 1 to 40 bar.

The invention relates to a process for preparing long-chainglycine-N,N-diacetic acid derivatives.

Glycine-N,N-diacetic acid derivatives can be employed as biodegradablecompleting agents for alkali metal and heavy metal ions.

Various processes for preparing these compounds are known.

WO 94/29421 describes processes for preparing glycine-N,N-diacetic acidderivatives. These entail converting long-chain aliphatic aldehydes withiminodiacetonitrile and HCN alkylglycinonitrile-N,N-diacetonitrile, theresulting compound being hydrolyzed. The compounds can likewise beobtained by reacting the aldehydes with HCN and ammonia to givesubstituted amino nitrites, which are hydrolyzed to substituted aminoacids, which is followed by reaction with formaldehyde and sodiumcyanide. The process is too complicated for some compounds because longreaction times are necessary. Moreover the yields of the requiredcompounds are still in need of improvement. The proposed processes arenot always suitable for transfer to the industrial scale.

DE-A 195 18 986 describes a process for preparing gly-cine-N,N-diaceticacid derivatives by reacting glycine derivatives or their precursorswith formaldehyde and hydrogen cyanide or reacting iminodiacetonitrileor iminodiacetic acid with appropriate aldehydes and hydrogen cyanide inaqueous acidic medium. The starting material employed in this case isthe unpurified crude material derived from the industrial synthesis ofglycine derivatives or their precursors or of iminodiacetonitrile oriminodiacetic acid, or mother liquors produced in syntheses of thesetypes. The process is carried out as indicated in WO 94/29421.

DE-A-195 18 187 relates to a process for preparing glycine-N,N-diaceticacid derivatives by reacting glycine derivatives or their precursorswith formaldehyde and alkali metal cyanide in aqueous alkali medium. Theprocess is likewise based on the process described in WO 94/29421, butfirstly from 0.5 to 30% of the amount of alkali metal cyanide requiredfor the reaction is added to the glycine derivatives or theirprecursors, and then the remaining amount of alkali metal cyanide andthe formaldehyde are metered in simultaneously over a period of from 0.5to 12 hours. Even this variant of the process cannot eliminate all theabovementioned disadvantages.

It is an object of the present invention to provide a process forpreparing glycine-N,N-diacetic acid derivatives by reactingiminodiacetonitrile with aldehydes and HCN or alkali metal cyanides,which avoids the abovementioned disadvantages and is suitable fortransfer to the industrial scale. The process ought to give high yieldsin short reaction times; it is additionally intended to providealternative processes which avoid the abovementioned disadvantages.

We have found that this object is achieved by processes with severalvariants as described below by means of component steps. Theglycine-N,N-diacetic acid derivatives can be obtained, for example, byreactions shown in the two reaction schemes detailed below.

The processes according to the invention are additionally explained bymeans of the reaction schemes depicted in the drawing, where

FIG. 1 shows reaction schemes A and B based on dode-canal as example and

FIG. 2 shows reactions schemes A1 and A2 for aldehydes of the formulaR—CHO, where R has the meaning indicated hereinafter. The object isachieved in particular by a process for preparing compounds of theformula IIb

 where R is C₆-C₃₀-alkyl or C₆-C₃₀-alkenyl, which may additionally haveupto 5 hydroxyl groups, formyl groups, C₁-C₄-alkoxy groups, phenoxygroups or C₁-C₄-alkoxycarbonyl groups as substituents and may beinterrupted by upto 5 nonadjacent oxygen atoms, or alkoxylate groups ofthe formula —(CH₂)_(k)—O—(A¹O)_(m)—(A²O)_(n)—Y where A¹ and A² are,independently of one another, 1,2-alkylene groups having 2 to 4 carbonatoms, Y is hydrogen, C₁-C₁₂-alkyl, phenyl or C₁-C₄-alkoxycarbonyl, andk is 1, 2 or 3, and m and n are each numbers from 0 to 50, and the totalof m+n must be at least 4,

 by reacting iminodiacetonitrile with aldehydes of the formula R—CHO andHCN or alkali metal cyanides, the process being carried out

 a) in the absence of an organic solvent and in the presence of a Lewisor Brönsted acid, or

 b) in the presence or absence of an organic solvent and in the presenceof an emulsifier, or

 c) in the presence or absence of an organic solvent and under apressure in the range from 1 to 40 bar.

It has been found according to the invention that is reactions withaldehydes and HCN or alkali cyanides, as well as the hydrolysis ofnitriles or amides to acids, can be speeded up and, moreover, the yieldis increased under an elevated pressure in the range from 1 to 40 bar,preferably from 1.5 to 30 bar, in particular from 2 to 15 bar. Thesepreferred pressure ranges also relate to the other reactions mentioned.Reaction of iminodiacetonitrile with aldehydes and HCN can moreover bespeeded up by reacting in the absence of an organic solvent and, inparticular, in the absence of further water in the reaction system, ie.by reacting without diluent and in the presence of a Lewis or Brönstedacid.

The reaction can additionally be carried out in the presence of anemulsifier, which is preferably employed in a concentration of from 1 to50 g/l, particularly preferably 2 to 30 g/l of reaction mixture.Emulsifiers which can be employed are all compounds suitable for thispurpose. Examples are anionic, cationic, amphoteric and nonionicemulsifiers. The lipophilic end groups of the emulsifiers are, as arule, straight-chain or branched alkyl radicals which may containunsaturated bonds, aryl radicals or alkylaryl radicals. Examples ofsuitable hydrophilic end groups for anionic emulsifiers are carboxylate,sulfonate, sulfate, phosphate, polyphosphate, lactate, citrate andtartrate. Suitable examples of cationic emulsifiers are amine salts andquaternary ammonium compounds. Suitable amphoteric emulsifiers arezwitterionic compounds of the amino acid type and, for example, betaine.Suitable for nonionic emulsifiers are residues of alcohols, polyethers,glcyerol, sorbitol, pentaerythritol, sucrose, acidic acid or lacticacid. The emulsifiers may additionally have hydrophilic groups inbetween such as hydroxyl, ester, sulfamide, amide, polyamide, polyamine,amine, ether, polyether, glycerol, sorbitol, pentaerythritol or sucrosegroups.

Examples of suitable emulsifiers are ethoxylation products and fattyacid condensation products, fatty alcohol ethoxylates and, whereappropriate, polyglycols and products of the reaction of phenols andoils with ethylene oxide.

The emulsifiers particularly employed are compounds such as alkali metalalkyl sulfates, in particular sodium dodecyl sulfate or mixtures ofhydrophobic alkyl sulfates. It is also possible to employ nonionicsurfactants such as fatty alcohol ethoxylates, which are, in particular,low-foaming.

The process step indicated above relates to process B for converting theinitial aldehyde into the compound of the formula IIb.

The invention also relates to a process for preparing compounds of theformula IIa

 where R has the abovementioned meaning, by reacting aldehydes of theformula R—CHO with HCN or alkali metal cyanides and ammonia in thepresence of an organic base, the reaction being carried out under apressure in the range from 1 to 40 bar. In FIG. 1, this reactioncorresponds to the conversion of the initial aldehyde into the compoundof the formula IIa.

The invention likewise relates to a process for preparing compounds ofthe formula IIb as defined above, by reacting compounds of the formulaIIa as are defined above and can be prepared by the above process, withformaldehyde and HCN or alkali metal cyanides, the process being carriedout in the presence or absence of a solvent under a pressure in therange from 1 to 40 bar. This reaction corresponds to the step forconverting the compound of the formula IIa into the compound of theformula IIb in FIG. 1.

The invention furthermore relates to a process for preparing compoundsof the formula IX

 where R has the abovementioned meaning, and M is hydrogen, alkalimetal, alkaline earth metal, ammonium or substituted ammonium in theappropriately stoichiometric amounts, by reacting compounds of theformula IIb as are defined above and can be prepared by an aboveprocess, with alkali metal hydroxide solutions with or without solutionswhich contain ions of M, the reaction with the alkali metal hydroxidesolutions being carried out under a pressure in the range from 1 to 40bar. This reaction corresponds to the process step from the compound ofthe formula IIb to the compound of the formula IXa in FIG. 1.

The invention further relates to a process for preparing compounds ofthe formula IV

 where R and M have the abovementioned meanings, by reacting compoundsof the formula IIa as are defined above and can be prepared by the aboveprocess, with sodium hydroxide solution, alkali metal hydroxidesolutions and, where appropriate, solutions which contain ions of M, inthe additional presence of aliphatic C₃₋₉ ketones, the reaction beingcarried out under a pressure in the range from 1 to 40 bar. Thisreaction step corresponds to the step for converting the compound of theformula IIa to the compound of the formula IV in FIGS. 1 and 2.

The invention additionally relates to a process for preparing compoundsof the formula IX as defined above, by reacting compounds of the formulaIV as are defined above and can be prepared by the above process, withformaldehyde and HCN or alkali metal cyanide and subsequent reactionwith alkali metal hydroxide solutions and reaction with solutions whichcontain ions of M, the reactions being carried out under a pressure inthe range from 1 to 40 bar. This reaction step is a step in FIGS. 1 and2 from the compound of the formula IV to the compound of the formulaIXa. Compounds of the formula IV can also be obtained by acidic oralkaline hydrolysis of hydantoins of the formula V

where R has the abovementioned meaning, it being possible to obtain thehydantoins by reacting, under atmospheric or superatmospheric pressure,aldehydes of the formula R—CHO with alkali metal cyanides and ammoniumcarbonate.

Besides the two process variants A and B (specific), the invention alsorelates to the following process variants B (general) C and D. In thisconnection, the invention relates to a process for preparing compoundsof the formula IX as defined above by reacting

(B) iminodiacetic acid compounds of the formula XI

X—CH₂—NH—CH₂—Y  (XI)

where X and Y are, independently, CO₂M, CO₂R¹

where R¹=C₁₋₁₂-alkyl, CONH₂ or CN,

(a) with aldehydes of the formula R—CHO and HCN or alkali metalcyanides, or

(b) with cyanohydrins of the formula R—CH(OH)CN, in the presence ofabsence of an organic solvent under a pressure in the range from 1 to 40bar, or

(C) glycine with aldehydes of the formula R—CHO and HCN or alkali metalcyanides with monosubstitution and subsequently with

(a) formaldehyde and HCN or alkali metal cyanides or

(b) HO—CH₂—CN

in the presence or absence of an organic solvent, it being possible tocarry out the reaction under a pressure of from 1 to 40 bar, or

(D) glycine with

(a) formaldehyde and HCN or alkali metal cyanide, or

(b) HO—CH₂—CN,

with monosubstitution and subsequently with aldehydes of the formulaR—CHO and HCN or alkali metal cyanide in the presence or absence of anorganic solvent, it being possible to carry out the reaction under apressure of from 1 to 40 bar,

where R in each case has the abovementioned meaning,

possibly followed by a hydrolysis of nitrile or amide functionalitieswhich are present, which can be carried out under a pressure of from 1to 40 bar.

Process variant C complies with the following scheme:

R—CHO+glycine+HCN→NC—CHR—NH—CH₂—COOHH₂CO+HCN→→NC—CHRN(CH₂CN)—COOH→compound of the formula IX.

Reaction sequence D complies with the following scheme:

Glycine+H₂CO+HCN→NC—CH₂—NH—CH₂—COOH+R—CHO+HCN→NC—CHR—N(CH₂—CN)—CH₂—COOH→compoundof the formula IX.

The processes detailed above can additionally be improved by using oneor more of the following process variants: use of antifoams use of phasetransfer catalysts, use of emulsifiers, temperature in the range from 20to 220° C., preferably 30 to 180° C., in particular 50 to 140° C., pH inthe range from 0 to 11. If the reactions are carried out undersuperatmospheric pressure, the pressure is preferably from 1.5 to 30bar, in particular 2 to 15 bar.

The invention furthermore relates to compounds which arise during thereaction schemes detailed above. These compounds have the formulaR—CHR²R³ selected from the compounds below

 where R′ is C₂₋₆-alkyl and R is C₆₋₂₀-alkenyl, excepting compounds ofthe formulae IV and V with R=C₁₇₋₂₀-alkenyl, of the formula I whereR=n−9-decenyl and of the formula VIII where R=C₆₋₁₀-alkenyl,

 or R is the radical R″O—CH₂—CH₂ where R″ is C₃₋₂₀-alkyl orC₃₋₂₀-alkenyl, excepting compounds of the formula IV with R″=C₅₋₂₀-alkyland of the formula X where R″=C₅₋₈-alkyl.

 The compounds are particularly those where R is C₁₂₋₂₀-alkenyl and R″is C₆₋₁₅-alkyl or C₃₋₁₂-alkenyl.

Before detailed description of the processes according to the invention,the compounds employed according to the invention are described indetail.

Suitable alkali metal, ammonium and substituted ammonium salts are, inparticular, the sodium, potassium and ammonium salts, and in the case ofthe compounds of the formula IX, in particular the trisodium,tripotassium and triammonium salt, and organic triamine salts with atertiary nitrogen atom.

Particularly suitable bases underlying the organic amine salts aretertiary amines such as trialkylamines having 1 to 4 carbon atoms in thealkyl, such as trimethyl- and triethylamine, and trialkanolamines having2 or 3 carbon atoms in the alkanol residue, preferably triethanolamine,tri-n-propanolamine or triisopropanolamine.

The alkaline earth metal salts which are particularly employed are thecalcium and magnesium salts.

Particularly suitable straight-chain or branched alk(en)yl radicals forthe R radical are C₆-C₂₀-alkyl and -alkenyl, and of these in particularstraight-chain radicals derived from saturated or unsaturated fattyacids. Examples of individual R radicals are: n-hexyl, n-heptyl,3-heptyl (derived from 2-ethylhexanoic acid), n-octyl, isooctyl (derivedfrom isononanoic acid), n-nonyl, n-decyl, n-undecyl, n-dodecyl,isododecyl (derived from isotridecanoic acid), n-tridecyl, n-tetradecyl,n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl,n-eicosyl and n-heptadecenyl (derived from oleic acid). Mixtures mayalso occur for R, in particular those derived from naturally occurringfatty acids and from synthetic industrial acids, for example thoseproduced by the oxo synthesis.

Particularly used as C₁-C₁₂-alkylene bridges A are polymethylene groupsof the formula —(CH₂)_(k)— where k is a number from 2 to 12, inparticular from 2 to 8, ie. 1,2-ethylene, 1,3-propylene, 1,4-butylene,pentamethylene, hexamethylene, heptamethylene, octamethylene,nonamethylene, decamethylene, undecamethylene and dodecamethylene.Hexamethylene, octamethylene, 1,2-ethylene and 1,4-butylene areparticularly preferred in this connection. However, it is also possiblefor branched C₁-C₁₂-alkylene groups to occur, for example—CH₂CH(CH₃)CH₂—, —CH₂C(CH₃)₂—CH₂—, —CH₂CH(C₂H₅)— or —CH₂CH(CH₃)—.

The C₆-C₃₀-alkyl and C₆-C₃₀-alkenyl groups may have upto 5, inparticular upto 3, additional substituents of the type mentioned, and beinterrupted by upto 5, in particular upto 3, nonadjacent oxygen atoms.Examples of such substituted alk(en)yl groups are —CH₂OH, —CH₂CH₂OH,—CH₂CH₂—O—CH₃, —CH₂CH₂—O—CH₂CH₂—O—CH₃, —CH₂—O—CH₂CH₃, —CH₂—O—CH₂CH₂—OH,—CH₂—CHO, —CH₂—OPh, —CH₂—COOCH₃ or —CH₂CH₂—COOCH₃.

Particularly suitable alkoxylate groups are those where m and n are eachnumbers from 0 to 30, especially from 0 to 15. A¹ and A² are groupsderived from butylene oxide and, especially, from propylene oxide andfrom ethylene oxide. Pure ethoxylates and propoxylates are of particularinterest, but ethylene oxide/propylene oxide block structures may alsooccur.

In the first place, process variant A which comprises two reactionroutes A1 and A2 as depicted in FIG. 2 will be explained.

The long-chain α-amino nitrites of the formula IIa can be prepared fromthe corresponding cyanohydrins and liquid ammonia or highly concentratedaqueous ammonia solutions (concentrations from 30 to 80% by weight) orfrom the corresponding long-chain aldehydes, hydrogen cyanide and liquidammonia or highly concentrated aqueous ammonia solutions. Startingmaterials which can be used besides pure compounds are the startingmaterials described in DE-A-195 18 986 from the industrial synthesis ofmonoaldehydes. Particularly used are mixtures of aldehydes or mixturesof aldehydes and the corresponding alcohols. In process variant A, thestarting materials are preferably those from the industrial synthesis ofα-amino nitrites, α-amino acids or their precursors, by which is meantthe underlying cyanohydrins or the corresponding aldehydes or thehydantoins substituted in position 5. Unpurified crude material or themother liquors produced are preferably employed.

Preferred embodiments of variant A:

Variant A

The α-amino nitrile of the formula IIa or the amino acid of the formulaIV is reacted with 1.8 to 3.0 eq, in particular 2.0 to 2.5 eq, ofhydrogen cyanide (HCN) and, simultaneously or sequentially, with 1.8 to3.0 eq, in particular 2.0 to 2.5 eq, of formaldehyde in water or amixture of water and a water-miscible organic solvent such as alcohols,ethers, etc., in particular alcohols such as methanol, ethanol,n-propanol, i-propanol, tert-butanol, with a water content of from 1 to99%, in particular 20 to 80%, at a pH of from 0 to 11, within from 0.5to 12 hours, in particular 1 to 5 hours. Stirring is then normallycontinued for from 0.5 to 20 hours, in particular 3 to 10 hours, underthe reaction conditions. The cyanomethylation can in both embodimentsalso be carried out stepwise and with isolation of the mono(cyanomethyl)stage. It is also possible to employ glycolonitrile in place offormaldehyde and hydrogen cyanide. Hydrolysis is subsequently carriedout, where appropriate after isolation of the intermediate product (XII)by filtration or decantation, normally in embodiment A2 with 2.4 to 6,in particular 3 to 5, and in embodiment A1 with 1.6 to 4, in particular2 to 3 mole equivalents of bases able to release hydroxide ions inaqueous medium, such as alkali metal hydroxides, ammonium hydroxides,barium hydroxide, calcium hydroxide or alkali metal alcoholates,preferably aqueous sodium or potassium hydroxide solution or alcoholicsodium or potassium hydroxide solution, for example ethanolic sodium orpotassium hydroxide solution, with an alcohol content of from 5 to 50%,in particular 10 to 40%, under a pressure of from 1 to 40 bar, inparticular 2 to 15 bar, and from 20 to 220° C., in particular from 30 to160° C. A particular embodiment of the hydrolysis comprises the ammoniawhich is produced being continuously decompressed to the set pressurethrough a relief valve when a preset pressure of from 1.5 and 10 bar, inparticular 2 to 6 bar is reached.

The hydrophobic α-amino nitrites are obtained according to the inventioneither from the corresponding cyanohydrins and from 1 to 10 eq, inparticular 3 to 8 eq, of liquid ammonia or 1 to 20 eq, in particular 3to 15 eq, of a highly concentrated aqueous ammonia solution, preferably30 to 80% strength ammonia, or directly from the underlyingmonoaldehydes, hydrogen cyanide and 1 to 10 eq, in particular 3 to 8 eq,of liquid ammonia or 1 to 20 eq of preferably 30 to 80% strength ammoniaunder a pressure of 1 to 40 bar, in particular 2 to 15 bar. Stirring isthen normally continued for from 0.1 to 12 h, in particular 0.5 to 6 h,at from 0 to 35° C. under the reaction conditions. The initialtemperature is preferably 0° C., which is gradually raised to 35° C.

When amino nitrites are synthesized by known methods in the case oflong-chain products the resulting reaction mixtures in some cases have avery high content of the. unwanted imino dinitriles which result fromthe reaction between 1 molecule each of α-aminonitrile and unreactedcyanohydrin and which may cause problems in subsequent reactions. Theyields of required product are then also frequently unsatisfactory anduneconomic.

Said technical improvements in the processes result in the amounts ofthese by-products being reduced to <5 mol % and, in the optimal case,production thereof being completely suppressed. A preferred embodimentproves to be reaction of the cyanohydrin either pure or in a suitableorganic solvent, in particular alcohols, in liquid ammonia.

Hydrolysis is subsequently carried out, where appropriate after phaseseparation, filtration or decantation, normally with 0.8 to 2, inparticular 1 to 1.5, mole equivalents of aqueous sodium or potassiumhydroxide solution or alcoholic sodium or potassium hydroxide solution,for example ethanolic sodium or potassium hydroxide solution with analcohol content of from 5 to 50%, in particular 10 to 40%, based onamino nitrile to be reacted, where appropriate under a pressure of from1 to 40 bar, in particular 2 to 15 bar, and from 20 to 220° C., inparticular 30 to 160° C.

The ammonia which is produced is continuously decompressed to the presetpressure through a relief valve when a preset pressure of from 1.5 to 10bar, in particular 2 to 6 bar, is reached.

Alternatively, the amino nitrites can be hydrolyzed to the amino acidsby saturated solution of hydrogen chloride in alcohols, in particularethanol etc. It has proven beneficial to carry out the hydrolysis in thepresence of substoichiometric amounts of alkali metal or alkaline earthmetal hydroxides, in particular aqueous sodium or potassium hydroxidesolution, with the addition of ketones, in particular acetone, startingthe hydrolysis at temperatures <30° C. It is possible by this procedureto suppress cleavage of the amino nitrites back to the aldehyde and tooptimize further the yields of amino acid. The α-amino amides initiallyobtained under mild reaction conditions can be either isolated andhydrolyzed further under normal hydrolysis conditions and under pressureor hydrolyzed further directly in the reaction solution after additionof appropriate amounts of aqueous alkali at elevated temperature andunder superatmospheric pressure. This mechanical improvement in theprocess for hydrolyzing hydrophobic amino nitrites is expedientlycarried out in such a way that the first reaction step takes place withthe addition of, preferably, 0.1 to 0.9, in particular 0.15 to 0.7, moleequivalents of alkali and 0.2 to 2, in particular 0.3 to 1, moleequivalents of the relevant ketone and from 5 to 40° C., in particular10 to 30° C. For the further hydrolysis to the amino acids, the alkalicontent is increased to stoichiometric amounts, and hydrolysis iscontinued under superatmospheric pressure.

The amino acids employed for preparing long-chain glycine-N,N-diaceticacids can, however, also be obtained by acidic or alkaline hydrolysisunder a pressure of from 1 to 40 bar of the 5-substituted hydantoinsobtainable from the corresponding aldehydes, alkali metal cyanide andammonium carbonate.

The cyanohydrins are normally prepared by known methods from thecorresponding aldehyde and hydrocyanic acid with addition of bases suchas triethylamine, alkali metal cyanides etc. without diluent or in thepresence of a suitable organic solvent, in particular of alcohols.

The long-chain monoaldehydes employed in variants A and B are preferablyderived from processes which can be carried out industrially to preparethem from easily available and low-cost basic chemicals, in particularhydroformylation reactions of corresponding α-olefins andmetal-catalyzed reductions of the underlying carboxylic acids andesters. It has proven particularly advantageous to employ mixtures ofaldehydes and alcohols as typically produced in a number of processes ofthis type. This makes it possible to dispense with addition of awater-miscible organic solvent such as methanol, ethanol, isopropanol,dioxane, etc. in the individual process steps. The alcohol which ispresent has not only solubilizing but also antifoam properties which maymake a very advantageous contribution to reducing the unwanted foamingdue to the evolution of ammonia at the hydrolysis stage. It isunnecessary to remove these alcohols from the product or the productproperties. Mixtures of isomeric and homologous aldehydes as areproduced in many industrial syntheses can also be reacted successfully.

The addition, according to the invention of a suitable emulsifier whichis able to disperse the aldehydes, cyanohydrins, amino nitrites, aminoamides or amino acids sufficiently well in the purely aqueous medium, ina concentration of 1 to 50 g/l of reaction mixture, in particular 2 to30 g/l, results in a marked reduction in the reaction times bycomparison with reaction without emulsifier. This variant of the processresults in reaction times like those which can be obtained in Streckerreactions on amino nitrites or amino acids under superatmosphericpressure at elevated temperatures in an autoclave. It is particularlybeneficial to carry out the reactions in the presence of an emulsifierunder superatmospheric pressure. Examples of emulsifiers which can beemployed successfully are sodium dodecyl sulfate, sodiumdodecylbenzenesulfonate (LAS) and mixtures of hydrophobic alkylsulfates. It is also possible to employ nonionic surfactants such asfatty alcohol ethoxylates, some of which are low-foam surfactants. Thereaction times are also reduced on use of phase transfer catalysts whichare able to bring about a rapid phase exchange between the hydrophobiccomponents of aldehydes, cyanohydrins, amino nitrites, amino amides oramino acids, formaldehyde and hydrogen cyanide, and sodium cyanide inthe aqueous or aqueous alcoholic system. Examples of phase transfercatalysts used are quaternary ammonium, phosphonium and other oniumcompounds, crown ethers and cryptands. Examples are tetraalkylammoniumsalts, trialkylbenzyl-ammonium salts, tetraalkylphosphonium salts andother corresponding quaternary salts.

In some variants of the processes described hereinbeforehand andhereinafter, the occurrence of foaming, in particular at the hydrolysisstage due to the ammonia which is produced, may cause problems. Additionof small or very small amounts of an antifoam, preferably a siliconeantifoam, results in collapse of the foam or a reduction to a minimumwhich can be satisfactorily controlled industrially. It is also possibleto employ other antifoam substances such as fatty alcohol ethoxylates,phosphoric esters etc. Addition of such substances is unnecessary if thereactions take place in aqueous alcoholic media, or mixtures oflong-chain aldehydes and corresponding alcohols are employed. Additionof surfactants such as alcohol alkoxylates is particularly advantageousbecause they remain in the product after the reaction has taken placeand can be employed in the mixture.

If the compounds IX result as salts, the free acids of the compounds IXcan be obtained by acidification by conventional methods.

Variant B

The reaction according to the invention of iminodiacetonitrile,iminodiacetic acid or their derivatives, in particular iminodiaceticesters or iminodiacetamides, with the appropriate long-chain aldehydesand hydrogen cyanide in embodiment B takes place either by reactingcrude iminodiacetonitrile or iminodiacetonitrile-containing motherliquors with the aldehyde and hydrocyanic acid to give the correspondingglycinonitrile-N,N-diacetonitrile, followed by alkaline hydrolysis tothe compounds IX under a pressure of from 1 to 40 bar, in particular 2to 15 bar, at from 20 to 220° C., in particular 50 to. 140° C., or byalkaline hydrolysis of the iminodiacetonitrile to the iminodiacetic acidand, where appropriate, its conversion into derivatives by knownmethods, in particular iminodiacetic esters or iminoacetamides, followedby reaction with the aldehyde and hydrocyanic acid under a pressure offrom 1 to 40 bar, in particular 2 to 15 bar and from 20 to 220° C., inparticular 50 to 140° C. Higher pressures are also possible, forexample, by injecting protective gas such as nitrogen.

The iminodiacetonitrile is often reacted as 5 to 30% by weight motherliquor with 0.8 to 5.0 eq, in particular 1 to 3 eq, of hydrogen cyanideand, simultaneously or sequentially, with 0.8 to 3.0 eq, in particular1.0 to 1.5 eq, of the long-chain aldehyde in water or a mixture of waterand a water-miscible organic solvent, in particular alcohols, with awater content of from 1 to 99%, in particular 20 to 80%, at a pH of,preferably, 0 to 5, which is normally adjusted by adding mineral acids,within from 1 to 15 hours, in particular 2 to 6 hours, undersuperatmospheric pressure in an autoclave. Stirring is then normallycontinued for 0.5 to 20 hours, in particular 3 to 10 hours, under thereaction conditions. Hydrolysis is ultimately carried out, ifappropriate after isolation of the intermediate by filtration ordecantation, normally with 2 to 5, in particular 3 to 4, mol equivalentsof bases able to release hydroxide ions in an aqueous medium, such asalkali metal hydroxides, ammonium hydroxides, barium hydroxide, calciumhydroxide or alkali metal alcoholates, preferably aqueous sodium orpotassium hydroxide solution or alcoholic sodium or potassium hydroxidesolution, in particular ethanolic sodium or potassium hydroxidesolution, with an alcohol content of from 5 to 50%, in particular 10 to40%, based on iminodiacetonitrile employed, under superatmosphericpressure. A particular embodiment of the hydrolysis consists incontinuously decompressing the ammonia which is produced to the presetpressure through a relief valve when a preset pressure of from 1.5 to 10bar, in particular 2 to 6 bar, is reached.

Variants C, D

The reaction according to the invention of unsubstituted glycine, itsprecursors or its secondary products cyanomethylglycine andcarboxymethylglycine, which are obtainable by monosubstitution ofglycine with formaldehyde and hydrogen cyanide, with the appropriatelong-chain aldehydes and hydrogen cyanide in embodiments C and D isnormally carried out under a pressure of from 1 to 40 bar, in particular2 to 15 bar, from 20 to 220° C., in particular 50 to 140° C. Higherpressures are also possible, for example by injecting protective gassuch as nitrogen. The pH of the aqueous or organic aqueous, inparticular alcoholic aqueous, reaction medium with a water content offrom 1 to 99%, in particular 20 to 80% is from 0 to 11, preferably 1 to10. Precursors of glycine mean, for example glycinonitrile.

The formaldehyde and the hydrogen cyanide are metered simultaneouslyinto glycine or its precursors at the stated reaction temperature andthe stated pH over a period of from 0.1 to 12 hours, in particular 0.15to 6 hours, especially 0.25 to 3 hours. Reaction is then normallyallowed to continue for 1 to 20 hours, preferably 2 to 10 hours, underthe reaction conditions.

In embodiment C it is expedient to employ per mol equivalent of glycineor its precursors used as starting material for the first substitutionstep from 1.0 to 1.05 eq of the long-chain aldehyde, preferably astechnical product, and 1.0 to 1.6, in particular 1.0 to 1.4, eq ofhydrogen cyanide, and for the second substitution step from 1.0 to 1.6eq, in particular 1.0 to 1.4 eq, of formaldehyde, preferably in the formof its aqueous solution which is about 30% by weight, and from 1.0 to1.6, in particular 1.0 to 1.4, eq of hydrogen cyanide. Normally used asstarting material are aqueous solutions of glycine or its precursorswith a glycine or precursor content of from 10 to 50% by weight, inparticular 25 to 45% by weight.

In embodiment D it is expedient to employ per mol equivalent of theglycine or its precursors used as starting material for the firstsubstitution step from 1.0 to 1.05 eq of formaldehyde, preferably in theform of its aqueous solution which is about 30% by weight, and from 1.0to 1.6, in particular 1.0 to 1.4, eq of hydrogen cyanide, and for thesecond substitution step from 1.0 to 1.6 eq, in particular 1.0 to 1.4eq, of the long-chain aldehyde, preferably as technical product, from1.0 to 1.6, in particular 1.0 to 1.4, eq of hydrogen cyanide.

The hydrolysis of nitrile functionalities which are present after thereaction to give carboxylate groups is normally carried out with from0.8 to 2.0, in particular 1.0 to 1.5, mol equivalents per nitrilefunctionality of aqueous sodium or potassium hydroxide solution oralcoholic sodium or potassium hydroxide solution, such as ethanolicsodium or potassium hydroxide solution with an alcohol content of from 5to 50%, in particular under pressures from 2 to 15 bar and at from 20 to220° C., in particular from 50 to 140° C. Higher pressures are alsopossible, for example by injecting protective gas such as nitrogen. Ithas proven to be particularly beneficial for the ammonia which isproduced to be continuously decompressed to the preset pressure througha relief valve when a preset pressure of from 1 to 10 bar, in particular2 to 6 bar, is reached.

In place of the long-chain aldehydes, formaldehyde and hydrogen cyanide,it is also possible for their synthetic equivalents, the correspondinghydrophobic cyanohydrins and glycolonitrile to be reacted in a similarway to the individual components in embodiments B, C or D.

By-products found in the particular hydrolysis solutions areoccasionally small amounts of the corresponding α-hydroxy carboxylicacids and fatty acids produced on hydrolysis with unreacted cyanohydrinor the cyanohydrin formed as intermediate from aldehyde and hydrogencyanide. Since these compounds have a beneficial effect on theproperties of the product, they need not be removed from the reactionmixtures, which is why costly and elaborate purification steps areunnecessary.

Addition according to the invention of a suitable emulsifier which isable to disperse the particular long-chain aldehyde sufficiently well inthe purely aqueous medium, in a concentration of from 1 to 50 g/l ofreaction mixture, in particular 2 to 30 g/l, results in a markedreduction in the reaction times in embodiments B to D compared withreaction without emulsifier. This technical improvement in the processresults in reaction times which are in the region of the Streckerreactions under superatmospheric pressure. Accordingly it isparticularly beneficial to carry out the reactions in the presence of anemulsifier under superatmospheric pressure. Examples of emulsifierswhich can be employed successfully are sodium dodecyl sulfate andmixtures of hydrophobic alkyl sulfates. The use of nonionic surfactantssuch as fatty alcohol ethoxylates and nonionic low-foam surfactants suchas specific fatty alcohol alkoxylates or mixtures of nonionicsurfactants and aldehydes equally has beneficial effects on the reactiontimes and yields as for variant A. These emulsifiers or surfactants mayalso remain in the product if required, and advantageously do not needto be removed because they may supplement or have a beneficial effect onthe product properties.

The reaction times are also reduced on use of phase transfer catalystswhich are able to bring about a rapid phase exchange between thelong-chain aldehyde, iminodiacetonitrile and hydrogen cyanide in theaqueous or aqueous alcoholic system or between the long-chain aldehyde,glycine, its precursors or its secondary products cyanomethylglycine andcarboxymethylglycine and hydrogen cyanide (variants C and D). Phasetransfer catalysts which are used are described above for variant A.

The preparation process without diluent is particularly preferred, thatis to say in the melt without use of additional solvents. In this case,the abovementioned emulsifiers are preferably employed. It is likewiseparticularly advantageous for the reaction to take place in the presenceof alcohols, which may also have an emulsifying effect. The hydrolysispreferably takes place under elevated pressure, with the reactionmixture being decompressed to the required pressure if a maximumpermissible pressure is exceeded. The preferred processes are explainedin detail by means of examples below. The preferred alcohols are alsoindicated therein.

The reaction can also be carried out in accordance with the meteringinstructions given in DE-A-195 18 987. Further procedures can be foundin WO 94/29421.

The invention is explained in detail by means of examples below.

EXAMPLES Example 1 D,L-2-Aminotridecanonitrile

27 g (1 mol) of hydrocyanic acid are metered over the course of 30minutes into a mixture of 190 g (1 mol) of 97% pure lauraldehyde and12.2 g (0.12 mol) of triethylamine at 15° C. in a steel autoclave underatmospheric pressure. The mixture is then heated at 40° C. for 2 hoursuntil aldehyde is no longer detectable in the IR spectrum. The reactoris closed, 73 g (4.3 mol) of liquid ammonia are condensed in at about25° C. This sets up a pressure of 12 bar. The mixture is then stirredunder the same conditions for 1 h before being decompressed toatmospheric pressure, the ammonia escaping. For stability reasons, theproduct is not worked up further but is reacted immediately. The contentis determined by GC, the yield of amino nitrile determined thereby being204 g (0.97 mol; 97% of theory).

Example 2 D,L-n-undecylalycine-N,N-diacetic acid

7.5 g (0.05 mol) of a 33% strength sodium cyanide solution are added toa solution of 59.1 g (0.25 mol) of 89% pure 2-aminotridecanonitrile fromExample 1 in 150 ml of ethanol in a steel autoclave. The reactor isclosed and then heated to 100° C. before simultaneously metering in 68.2g (0.46 mol) of a 33% strength sodium cyanide solution and 51 g (0.51mol) of a 30% strength formaldehyde solution over the course of 1 h. Themixture is stirred at the same temperature under a pressure of about 4bar for 3 h until no further change in the cyanide content can be foundby titration. After addition of 20 g (0.25 mol) of 50% strength sodiumhydroxide solution, the reaction solution is hydrolyzed further at 100°C. under about 4 bar for 6 h. After cooling and decompression toatmospheric pressure, the volatile constituents are distilled off andthe residue is taken up in water. The pH is then adjusted to 2 withconcentrated hydrochloric acid, and the precipitate which forms isisolated by filtration. 82.6 g (0.23 mol) of 97% pureD,L-n-undecylglycinediacetic acid with a calcium binding capacity of2.81 mmol/g are obtained, corresponding to a yield of 93% of theory.

Example 3 D,L-2-aminotridecanoic acid

6.4 g (0.11 mol) of acetone and 4 g (0.05 mol) of 50% strength sodiumhydroxide solution are added successively to 105.2 g (0.25 mol) of a 50%strength solution of D,L-2-aminotridecanonitrile in ethanol at 10° C. ina steel autoclave. After warming to room temperature, the mixture isstirred for 30 minutes before being diluted with 50 ml of water, and afurther 16 g (0.2 mol) of 50% strength sodium hydroxide solution aremetered in. The reactor is closed and heated at 160° C. for 30 min, apressure of about 15 bar being set up. After cooling to room temperatureand decompression to atmospheric pressure, the volatile constituents aredistilled off and the residue is taken up in water. The pH is thenadjusted to 5 with concentrated hydrochloric acid, and the precipitatewhich forms is isolated by filtration. 50.3 g (0.22 mol; 88% of theory)of D,L-2-aminotridecanoic acid are obtained.

Example 4 D,L-n-undecylglycine-N,N-diacetic acid

57.3 g (0.25 mol) of 2-aminotridecanoic acid from Example 3 are added toa mixture of 250 g of water and 100 g of ethanol in a steel autoclave.51 g (0.51 mol) of a 30% strength formaldehyde solution are added tothis at room temperature under atmospheric pressure. The mixture is thenstirred for 1 h, before the reactor is closed and heated to 100° C. Apressure of about 4 bar is set up and, under this, 75.7 g (0.51 mol) ofa 33% strength sodium cyanide solution are metered in. The mixture isstirred further under the above conditions for 3 h until no furtherchange in the cyanide content can be found by titration. The pH isadjusted to 13 with 50% strength sodium hydroxide solution, after whichhydrolysis is continued under superatmospheric pressure for 6 h. Aftercooling and decompression to atmospheric pressure, the volatileconstituents are distilled off and the residue is taken up in water. ThepH is adjusted to 2 with concentrated hydrochloric acid, and theprecipitate which forms is isolated by filtration. 83.2 g (0.23 mol) of95% pure D,L-n-undecylglycine-N,N-diacetic acid with a calcium bindingcapacity of 2.75 mmol/g are obtained, corresponding to a yield of 92% oftheory.

Example 5 D,L-n-undecylglycinonitrile-N,N-diacetonitrile

A suspension of 71.3 g (0.75 mol) of 99% pure iminodiacetonitrile in 150g of water and 100 g of methanol in a steel autoclave is adjusted to pH1.0 with 7.5 g of 50% strength sulfuric acid. 31 g (1.14 mol) ofhydrocyanic acid are added dropwise to this at room temperature, beforethe autoclave is closed and warmed to 35 to 40° C. 142.5 g (0.75 mol) of97% pure lauraldehyde in 50 g of methanol are metered in by a diaphragmpump over the course of 1.5 h. The mixture is heated to 100° C. andstirred at the same temperature under a pressure of about 3.5 bar for 8hours until no further change in the hydrocyanic acid content can befound by titration. After cooling to 10° C., the phase containing theD,L-n-undecyl-glycinonitrile-N,N-diacetonitrile which has formed isseparated from the aqueous phase, and all volatile constituents areremoved. Recrystallization from a little ethanol results in 192.7 g(0.67 mol; 89% of theory) of trinitrile, whose purity is determined bygas chromatography.

Example 6 D,L-n-undecylglycinonitrile-N,N-diacetonitrile

A suspension of 71.3 g (0.75 mol) of 99% pure iminodiacetonitrile in 150g of water and 100 g of methanol in a steel autoclave is adjusted to pH1.0 with 7.5 g of 50% strength sulfuric acid. 23 g (0.83 mol) ofhydrocyanic acid are added dropwise to this at room temperature, beforethe autoclave is closed and warmed to 35 to 40° C. 142.5 g (0.75 mol) of97% pure lauraldehyde in 50 g of methanol are metered in by a diaphragmpump over the course of 1.5 h. The mixture is heated to 130° C. andstirred at the same temperature under a pressure of about 6 bar for 6hours until no further change in the hydrocyanic acid content can befound by titration. After cooling to 10° C., the phase containing theD,L-n-undecyl-glycinonitrile-N,N-diacetonitrile which has formed isseparated from the aqueous phase, and all volatile constituents areremoved. Recrystallization from a little ethanol results in 197 g (0.68mol; 91% of theory) of trinitrile, whose purity is determined by gaschromatography.

Example 7 D,L-n-undecylglycinonitrile-N,N-diacetonitrile

An emulsion of 48.0 g (0.5 mol) of 99% pure iminodiacetonitrile and 9.0g of sodium dodecyl sulfate in 185 g of water is adjusted to pH 1.0 with10.6 g of 50% strength sulfuric acid. 19 g (0.7 mol) of hydrocyanic acidare added dropwise to this at room temperature, before 95 g (0.5 mol) of97% pure lauraldehyde are metered in at 40° C. over the course of 2hours. The mixture is heated to 70° C. and stirred at the sametemperature for 6 hours until no further change in the hydrocyanic acidcontent can be found by titration. Phase separation starts during thisreaction. After cooling to 10° C., the phase containing the trinitrileis separated from the aqueous phase and recrystallized from a littleethanol. 124 g (0.43 mol; 86% of theory) of D,L-undecylglycinonitrileare obtained, it being impossible to remove the emulsifier completely,and its yield being determined by gas chromatography.

Example 8 D,L-n-undecylplycinonitrile-N,N-diacetonitrile

48 g (0.5 mol) of 99% pure iminodiacetonitrile, 95 g (0.5 mol) of 97%pure lauraldehyde, 1.6 g of p-toluene-sulfonic acid monohydrate and 19 g(0.7 mol) of hydrocyanic acid are mixed in a flask with an efficientcondenser at room temperature. The mixture is slowly heated to 70° C.and then stirred at this temperature for 3 hours until no further changein the hydrocyanic acid content can be found by titration. The crudereaction mixture is added to water, and the organic phase is separatedoff and recrystallized from a little ethanol. The yield ofD,L-undecylglycinonitrile-N,N-diacetonitrile is 127 g (0.44 mol; 88% oftheory), determined by gas chromatography.

Example 9 D,L-n-undecylglycine-N-N-diacetic acid

The partially crystalline mixture from Example 5 is introduced into 400ml of ethanol in a steel autoclave. 536 g (2.68 mol) of 20% strengthsodium hydroxide solution are added dropwise to this, and the mixture isstirred at 30° C. for 1 h. The autoclave is closed and then heated to100° C., and hydrolysis is continued at this temperature under apressure of about 4 bar for 6 h. After cooling to room temperature anddecompression to atmospheric pressure, the volatile constituents aredistilled off and the residue is taken up in water. The pH is adjustedto 2 with concentrated hydrochloric acid, and the precipitate whichforms is isolated by filtration. 231 g (0.64 mol) of 95% pureD,L-n-undecylglycinediacetic acid with a calcium binding capacity of2.75 mmol/g are obtained, corresponding to a yield of 96% of theory (85%of theory based on iminodiacetonitrile).

It is also possible to employ mixtures from Examples 6, 7 or 8 in placeof the mixture from Example 5.

We claim:
 1. A process for preparing compounds of the formula IIb:

wherein R is C₆-C₃₀-alkyl or C₆-C₃₀-alkenyl, which may additionally haveup to 5 hydroxyl groups, formyl groups, C₁-C₄-alkoxy groups, phenoxygroups or C₁-C₄-alkoxycarbonyl groups as substituents and may beinterrupted by up to 5 nonadjacent oxygen atoms, or alkoxylate groups ofthe formula —(CH₂)_(k)—O—(A¹O)_(m)—(A²O)_(n)—Y, wherein A¹ and A² are,independently of one another, 1,2-alkylene groups having 2 to 4 carbonatoms, Y is hydrogen, C₁-C₁₂-alkyl, phenyl or C₁-C₄-alkoxycarbonyl, andk is 1, 2 or 3, and m and n are each numbers ranging from 0 to 50, andthe total of m+n must be at least 4, comprising: reactingiminodiacetonitrile with an aldehyde of the formula R—CHO and HCN or analkali metal cyanide, wherein the process is conducted (a) in theabsence of an organic solvent by reacting without diluent and in thepresence of a Lewis or Brönsted acid, or (b) in the presence or absenceof an organic solvent and in the presence of an emulsifier, or (c) inthe presence or absence of an organic solvent and under a pressure inthe range from 2 to 15 bar.
 2. A process for preparing compounds of theof the formula IIb:

wherein R is C₆-C₃₀-alkyl or C₆-C₃₀-alkenyl, which may additionally haveup to 5 hydroxyl groups, formyl groups, C₁-C₄-alkoxy groups, phenoxygroups or C₁-C₄-alkoxycarbonyl groups as substituents and may beinterrupted by up to 5 nonadjacent oxygen atoms, or alkoxylate groups ofthe formula (CH₂)_(k)—O—(A¹O)_(m)—(A²O)_(n)—Y, wherein A¹ and A² are,independently of one another, 1,2-alkylene groups having 2 to 4 carbonatoms, Y is hydrogen, C₁-C₁₂-alkyl, phenyl or C₁-C₄-alkoxycarbonyl, andk is 1, 2 or 3, and m and n are each numbers from 0 to 50, and the totalof m+n must be at least 4, comprising: reacting a compound of theformula IIa:

with formaldehyde and HCN or an alkali metal cyanide, wherein theprocess is carried out in the presence or absence of a solvent under apressure in the range from 1 to 40 bar.